The goal of this research program is to identify and measure the forms in which human growth hormone (hGH), a family of peptides, circulate; to study the mode of action of each form in humans; and, recently, to attempt to extend this concept to human prolactin. We have made progress with three novel radioimmunoassays in the pursuit of these goals. The first two of these were conceived as approaches to differential measurement between the major 191 amino acid (AA) form of hGH and its 176 AA variant hGH20K. An RIA to hGH 32-46, unique to hGH itself, measures hGH only when the large loop is disrupted by reduction or carboxymethylation. However, hGH 32-46 improves glucose tolerance in some mouse strains and the RIA measures a low molecular weight naturally occurring pituitary gland peptide and, if trasylol is added, a small plasma component as well. The peptide which flanks hGH 32-46 and is, in its whole, unique to hGH20K, was also synthesized with slight modification. The analog of hGH20K (28-38) structure follows: 28 29 30 31 32 33 34 35 36 37 38 *Cys-Try-Gln-Glu-Phe-Asn-Pro-Gln-Thr-Ser-Leu-Cys S - S The Cys* was introduced to cyclize the peptide; it was considered that its juxtaposition to the tyrosine would keep it from being "read" in its use as hapten coupled to BSA. The RIA discloses that this portion of hGH20K is masked unless the large loop is broken either by chymotrypsinlike cleavage or by reduction of the S-S bridge. When either of these are done, the hGH20K reacts with displacement of the 125I-synthetic analog from its antibody, giving promise that we shall be able to measure hGH20K in plasma and to explore its possible physiological role.